Antimicrobial resistance: No action today, no cure tomorrow

The use of antimicrobial drugs to treat infection and disease has, over the past 70 years, changed the course of medical and human history. Now, those discoveries and the generations of drugs that followed them are at risk, as high levels of drug resistance threaten their effectiveness, according to the World Health Organization (WHO) which calls upon governments, health professionals, industry and civil society, and patients worldwide to slow down and restrict the unnecessary use of antibiotics in order to tackle microbial resistance.

“The world is on the brink of losing these miracle cures,” WHO Director-General Margaret Chan, M.D., said in a news release issued on World Health Day (April 7). “In the absence of urgent corrective and protective actions, the world is heading towards a post-antibiotic era, in which many common infections will no longer have a cure and, once again, kill unabated.”

The warning is more sobering with the knowledge that less than 5 percent of products currently in the research and development pipeline are antibiotic drugs.

“Antibacterial drug discovery is the most difficulty area of discovery,” Jeffrey Stein, Ph.D., president and CEO of the biotech company Trius Therapeutics, said during a recent press conference.“You don’t see a lot of large pharmaceutical companies taking these risks.”

Daniel Burgess, president and CEO of Mpex Pharmaceuticals, who was also on hand, said, “We don’t have hundreds of thousands of people dying of infection today,” said “The concern is the panic is going to be there in five to seven years … and, are we going to have effective treatments.”

In general, there are three ways to convey antimicrobial resistance (AMR):

• Develop a new class of drug that disease agents have never encountered (great in theory but in reality hard to accomplish);

• Overwhelm bacteria with high levels of antibiotics at the site of infection and

• Make existing therapies potent again (a cocktail approach that combines two or more drugs)

Mpex is in the final stage of clinical testing of a proprietary inhalable formulation of levofloxacin (a therapy currently taken orally) for the treatment of microbial infections in patients with cystic fibrosis who are prone to chronic respiratory infections.

Trius Therapeutics is in the final stage of clinical development of a next-generation antibiotic for intravenous and oral treatment of acute bacterial skin and skin-structure infections, and for the treatment of gram-positive infections including methicillin-resistant Staphylococcus aureus (MRSA).

Both Burgess and Stein’s remarks came during a presentation highlighting San Diego research efforts to combat antimicrobial resistance. Coinciding with World Health Day, the panel was held at the Sanford Burnham Medical Research Institute, and included opening remarks by Joe Panetta, president of CEO of BIOCOM.

Also presenting was Andrei Osterman, Ph.D., associate professor of bioinformatics and systems biology at Sanford Burnham. Osterman’s research focuses on discovering the molecular mechanisms of disease, the starting point for understanding what contributes to bacterial resistance. Osterman and his colleagues are looking for molecular weaknesses that can be exploited to attack resistant bacteria.

When it comes to AMR, “we are scared, but not scared enough,” he said. “But, we are at a moment when we can do a lot.”

Action to address AMR is taking place both in the laboratory and on the legislative front.

Currently working its way through Congress is H.R. 6331 – The GAIN Act (Generating Antibiotic Incentives Now) — which seeks to stimulate antibiotic development and related diagnostics by extending the exclusivity period for new qualified infectious disease products, gives priority regulatory review to applications for these kinds of products, and requires ongoing review of FDA guidelines for conducting clinical trials for antibiotics.